Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
Mol Cell Biol. 2022 Jan 20;42(1):e0046721. doi: 10.1128/MCB.00467-21. Epub 2021 Nov 1.
A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-κB pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality. A prior study showed that activin A could decrease viral load, which indicated there might be a risk to giving COVID-19 patients an inhibitor of activin. To evaluate this, the role for activin A was examined in a hamster model of SARS-CoV-2 infection, via blockade of activin A signaling. The hamster model demonstrated that use of an anti-activin A antibody did not worsen the disease and there was no evidence for increase in lung viral load and pathology. The study indicates blockade of activin signaling may be beneficial in treating COVID-19 patients experiencing ARDS.
一组住院的 COVID-19 患者，特别是老年人和合并症患者，会发展为疾病的最严重形式，其特征为急性呼吸窘迫综合征（ARDS），同时伴有“细胞因子风暴”。在这里，我们证明激活 NF-κB 途径的细胞因子可以诱导激活素 A。入院时激活素 A、激活素 B 和 FLRG 升高的患者与 COVID-19 的最严重结局相关，包括需要机械通气和全因死亡率。先前的一项研究表明，激活素 A 可以降低病毒载量，这表明给 COVID-19 患者使用激活素抑制剂可能存在风险。为了评估这一点，通过阻断激活素 A 信号通路，在 SARS-CoV-2 感染的仓鼠模型中检查了激活素 A 的作用。仓鼠模型表明，使用抗激活素 A 抗体不会使疾病恶化，并且没有证据表明肺病毒载量和病理学增加。该研究表明，阻断激活素信号可能有益于治疗发生 ARDS 的 COVID-19 患者。
